Osthole suppresses BACE-1 expression by up-regulating miR-9 in Alzheimer's disease / 中国药理学通报

ABSTRACT

Aim: To explore the mechanism of osthole regulating the expression of miR-9 to delay the occurance of Alzheimer' s disease (AD). Methods: The miRNA which expressed differently with osthole treatment was selected by microarray; the target gene binding to miRNA-9 was verified by databases and Cytoscape; the SH-SY5Y cells with over expression of APP were established using Lipofectamine2000. The cell viability was determined by MTT assay. The miRNA-9 inhibitor was transfected into cells, and the expression of miRNA-9 and BACE-1 mRNA was determined by RT-PCR; the changes of BACE-1 protein were determined by Western blot. Results: The results of database showed that osthole-mediated miRNA-9 was combined with BACE-1 genes. Our lab had established SH-SY5Y cells with over expression of APP. The results of MTT assay showed that 50 p,mol · L-1 osthole had a protective effect on cells. Osthole could increase the expression of miRNA-9, and the expression of miR- 9 was lowest in inhibitor group determined by RT- PCR. Osthole decreased the expression of BACE-1 mRNA and protein compared with APP group, and the expression of BACE-1 was highest in inhibitor group. Conclusion: Osthole plays a protective role in AD partly through suppressing the expression of BACE-1 by up-regulating miRNA-9.